In this reporting period, we conducted two studies. 1) First project focused on the phenomenon of unrealistic optimism. Researchers worry that patients in early-phase research experience unrealistic optimism about benefits and risks of participation. The standard measure of unrealistic optimism is the Comparative Risk/Benefit Assessment (CRBA) questionnaire which asks people to estimate their chances of an outcome relative to others in similar situations. Such a comparative framework may not be a natural way for research participants to think about their chances. The goal of this study was to examine how people interpret questions measuring unrealistic optimism and how their interpretations are associated with their responses. We used an early-phase cancer trial vignette to administer the CRBA to 297 adults from the general public. They estimated their comparative chances of risk and benefit (7- point scale: -3 less likely to +3 more likely), then provided rationales for their estimates. We found that for both CRBA benefit and risk questions, about 50% of respondents chose 0 (the correct response of average likelihood), and 50% chose a non-0 response. Respondents rationales for their estimates showed that overall only about 40-44% gave comparative rationales, indicating that they interpreted the CRBA as intended. 68.7% of respondents who gave the correct 0 rating gave comparative rationales, whereas only 11.6% of respondents who gave non-0 ratings did so. A similar trend was seen for chances of risk (p<0.001 for both). We concluded that research participants may not understand comparative benefit and risk questions as intended; attributions of unrealistic optimism may require additional evidence that the respondents estimates are intended to be comparative. A MS from this has been accepted for publication at J of Medical Ethics. 2) The second project's primary investigator was Christine Grady. We conducted a study of understanding and motivations for participation in sickle cell disease (SCD) gene transfer and stem cell transplant trials, interviewing 26 enrollees and decliners of these trials conducted at the NIH. This was a qualitative study using in depth interviews, which explored patients' understanding, their past experiences with SCD, deliberative processes about participation decisions, social and spiritual supports, and retrospective reflections for those who have already undergone the interventions. A MS from this study is in preparation.